Search for: [Abstract = "Further experiments showed that suppressive activity can be adoptively transferred by cells isolated from the inguinal and auxiliary lymph node cells and spleens of EC immunized mice. Suppression could be transferred with as 4x105 peripheral lymph node cells. Further, the effects of skin\-induced suppression was found to decline with time. However, neither mesenteric lymph node cells or thymocytes could transfer EC induced tolerance. Depletion experiments using anti\-TCRβ or anti\-TCRδ monoclonal antibodies \(mAb\) and complement revealed that EC induced suppressor cells belong to the population of TCRαβ\+ lymphocytes. To identify the phenotype of EC induced regulatory cells more precisely, total lymph node cells from mice EC tolerized with COLL II were depleted of either CD4 or CD8 T cells by treatment with mAb and complement prior to transfer into syngeneic DBA\/1 recipients. Protection was abrogated when either CD4 or CD8 T cells were depleted. Combining CD4\-depleted lymphocytes with CD8\-depleted lymphocytes, thereby reconstituting the populations of single\-positive cells, did not restore protection from disease, suggest that EC\-induced T regulatory cells co\-express both CD4 and CD8 coreceptors. In summary, these data suggest that EC immunization with COLL II induces a population of regulatory T cells with a TCRαβ\+ CD4\+ CD8\+ phenotype. Surprisingly, suppression was not specific to antigen, as EC immunization with any tested protein antigen \(COLL II, OVA or MBP\) prior to induction of CIA reduced disease severity. To determine the mechanism of EC induced suppression in CIA, the expression of pro\- and anti\-inflammatory cytokines by lymph node cells isolated from treated mice was investigated. These experiments showed that EC immunization with COLL II does not affect production of IL\-4, IL\-6, IL\-10, IL\-17E, TGF\-β or IFN\-γ when compared to DPBS\-treated animals. However, production of IL\-17A and TNF\-α was significantly increased. In vivo neutralization of IL\-17 abolished EC induced protection from the disease, which correlated with increased MPO activity and upregulated production of anti\-COLL II IgG2a antibodies. In the final part of the study, it was shown that transfer of EC induced T regulatory cells either before or after induction of CIA suppressed disease. Moreover, EC treatment of mice with COLL II after first signs of CIA caused partial recovery from disease, suggesting that this method might be useful to treat ongoing disease. In Summary, induction of immune tolerance via EC immunization could potentially be used to prevent and possibly treat RA and other autoimmune disorders. The noninvasive application of protein antigen to the skin and the ability to induce antigen nonspecific T regulatory cells makes EC immunization an attractive potential therapy."]

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